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通过向小鼠肝脏定向递送转座子分离永生化肝细胞系的潜力。

Potential for Isolation of Immortalized Hepatocyte Cell Lines by Liver-Directed Gene Delivery of Transposons in Mice.

作者信息

Sato Masahiro, Saitoh Issei, Inada Emi, Nakamura Shingo, Watanabe Satoshi

机构信息

Section of Gene Expression Regulation, Frontier Science Research Center, Kagoshima University, Kagoshima 890-8544, Japan.

Division of Pediatric Dentistry, Graduate School of Medical and Dental Science, Niigata University, Niigata 951-8514, Japan.

出版信息

Stem Cells Int. 2019 Jun 2;2019:5129526. doi: 10.1155/2019/5129526. eCollection 2019.

DOI:10.1155/2019/5129526
PMID:31281376
原文链接:https://pmc.ncbi.nlm.nih.gov/articles/PMC6589260/
Abstract

Isolation of hepatocytes and their culture represent important avenues to explore the function of such cells. However, these studies are often difficult to perform because of the inability of hepatocytes to proliferate . Immortalization of isolated hepatocytes is thus an important step toward continuous culture. For cellular immortalization, integration of relevant genes into the host chromosomes is a prerequisite. Transposons, which are mobile genetic elements, are known to facilitate integration of genes of interest (GOI) into chromosomes and . Here, we proposed that a combination of transposon- and liver-directed introduction of nucleic acids may confer acquisition of unlimited cellular proliferative potential on hepatocytes, enabling the possible isolation of immortalized hepatocyte cell lines, which has often failed using more traditional immortalization methods.

摘要

肝细胞的分离及其培养是探索此类细胞功能的重要途径。然而,由于肝细胞无法增殖,这些研究往往难以开展。因此,分离的肝细胞永生化是实现连续培养的重要一步。对于细胞永生化而言,将相关基因整合到宿主染色体是一个先决条件。转座子作为可移动的遗传元件,已知其有助于将目的基因(GOI)整合到染色体中。在此,我们提出,转座子与肝脏定向核酸导入相结合,可能赋予肝细胞无限的细胞增殖潜能,从而有可能分离出永生化肝细胞系,而使用更传统的永生化方法往往无法做到这一点。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/2ec4/6589260/1b86a745534a/SCI2019-5129526.004.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/2ec4/6589260/ffd39c057291/SCI2019-5129526.001.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/2ec4/6589260/23999391132b/SCI2019-5129526.002.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/2ec4/6589260/67c797d6b0f0/SCI2019-5129526.003.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/2ec4/6589260/1b86a745534a/SCI2019-5129526.004.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/2ec4/6589260/ffd39c057291/SCI2019-5129526.001.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/2ec4/6589260/23999391132b/SCI2019-5129526.002.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/2ec4/6589260/67c797d6b0f0/SCI2019-5129526.003.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/2ec4/6589260/1b86a745534a/SCI2019-5129526.004.jpg

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Int J Mol Sci. 2018 Nov 2;19(11):3452. doi: 10.3390/ijms19113452.
2
Establishment of Immortalized Human Hepatocytes by Introduction of HPV16 E6/E7 and hTERT as Cell Sources for Liver Cell-Based Therapy.通过导入人乳头瘤病毒16型E6/E7和人端粒酶逆转录酶建立永生化人肝细胞作为基于肝细胞治疗的细胞来源
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Concise Review: Advances in Generating Hepatocytes from Pluripotent Stem Cells for Translational Medicine.
简明综述:多能干细胞生成肝细胞用于转化医学的研究进展
Stem Cells. 2016 Jun;34(6):1421-6. doi: 10.1002/stem.2368. Epub 2016 Apr 22.
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Transplantation of a human iPSC-derived hepatocyte sheet increases survival in mice with acute liver failure.人诱导多能干细胞源性肝细胞片移植可提高急性肝衰竭小鼠的存活率。
J Hepatol. 2016 May;64(5):1068-1075. doi: 10.1016/j.jhep.2016.01.004. Epub 2016 Jan 14.
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Tracking and transforming neocortical progenitors by CRISPR/Cas9 gene targeting and piggyBac transposase lineage labeling.通过CRISPR/Cas9基因靶向和piggyBac转座酶谱系标记追踪和转化新皮质祖细胞。
Development. 2015 Oct 15;142(20):3601-11. doi: 10.1242/dev.118836. Epub 2015 Sep 23.
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piggyBac-ing models and new therapeutic strategies.piggyBac插入模型与新的治疗策略。
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